Tertiary centre study highlights low inpatient deintensification and risks associated with adverse outcomes in frail people with diabetes

Introduction The community deintensification rates in older people with diabetes are low and hospital admission presents an opportunity for medication review. We audited the inpatient assessment and deintensification rate in people with diabetes and frailty. We also identified factors associated with adverse inpatient outcomes. Methods A retrospective review of electronic charts was conducted in all people with diabetes and clinical frailty score ≥6 who were discharged from the medical unit in 2022. Data on demographics, comorbidities and background glucose-lowering medications were collected. Results Six-hundred-and-sixty-five people with diabetes and moderate/severe frailty were included in our analysis. For people with no HbA1c in the last six months preceding admission, only 9.0% had it assessed during inpatient. Deintensification rates were 19.1%. Factors that were associated with adverse inpatient outcomes included inpatient hypoglycaemia, non-White ethnicity, and being overtreated (HbA1c <7.0% [53 mmol/mol] with any glucose-lowering medication). Conclusion The assessment and deintensification rate in secondary care for people with diabetes and frailty is low. Inpatient hypoglycaemia, non-White ethnicity, and overtreatment are important factors in determining inpatient outcomes highlighting the importance of deintensification and the need for an evidence-based risk stratification tool.

Introduction: The community deintensification rates in older people with diabetes are low and hospital admission presents an opportunity for medication review.We audited the inpatient assessment and deintensification rate in people with diabetes and frailty.We also identified factors associated with adverse inpatient outcomes.Methods: A retrospective review of electronic charts was conducted in all people with diabetes and clinical frailty score ≥ 6 who were discharged from the medical unit in 2022.Data on demographics, comorbidities and background glucose-lowering medications were collected.Results: Six-hundred-and-sixty-five people with diabetes and moderate/severe frailty were included in our analysis.For people with no HbA1c in the last six months preceding admission, only 9.0% had it assessed during inpatient.Deintensification rates were 19.1%.Factors that were associated with adverse inpatient outcomes included inpatient hypoglycaemia, non-White ethnicity, and being overtreated (HbA1c < 7.0% [53 mmol/mol] with any glucose-lowering medication).

Conclusion:
The assessment and deintensification rate in secondary care for people with diabetes and frailty is low.Inpatient hypoglycaemia, non-White ethnicity, and overtreatment are important factors in determining inpatient outcomes highlighting the importance of deintensification and the need for an evidence-based risk stratification tool.

What is already known?
• People with diabetes and frailty require less intensive treatment due to the risks of hypoglycaemia, falls, and hospital admission.• Treatment inertia represents a significant issue in this cohort of population with studies showing low rates of community deintensification for people with diabetes and frailty.

What are the questions?
• What is the quality of inpatient assessment and management of people with diabetes and frailty?

Introduction
Approximately 40% of adults older than 65 years have diabetes and managing diabetes in this age group comes with distinct challenges. 1 Increasing evidence has shown that the degree of frailty, rather than age, is a better prognostic marker for people with diabetes. 2 , 3ssessment of frailty is recommended in people with diabetes and is being increasingly adopted in routine clinical practice, with several validated tools recommended by the Joint British Diabetes Societies (JBDS) ( Table 1 ) including the clinical frailty scale (CFS). 4When interpreting the CFS, it is crucial to understand that not all older adults are frail as frailty is a complex and dynamic condition that can occur at any age. 5Achieving tight glycaemic control can delay the long-term macro-and microvascular complications of diabetes, but it is important to strike a balance between potential benefits and associated risks.Tight glycaemic control in adults with frailty can be controversial due to increased risks of falls, hypoglycaemia, emergency department visits, hospitalisation, and mortality.Decisions regarding the deintensification of glucose-lowering medications in frail populations should be individualised and based on a thorough assessment of the patient's overall health, frailty status, life expectancy, and quality of life goals. 2 , 3eatment inertia is defined as the failure of healthcare professionals to intensify or deintensify treatment when it is indicated. 6The importance of deintensification in people with diabetes and frailty has been increasingly highlighted due to increasing polypharmacy, endocrine deficits, suboptimal food and drink intake, cognitive impairment, cardiovascular disease, and renal dysfunction, that increase susceptibility to hypoglycaemia and its potentially severe consequences. 7Moreover, whilst there is good evidence that tight glycaemic control can delay diabetes complications, evidence in people with diabetes and frailty is lacking.][10] The evidence regarding deintensification in people with diabetes and frailty beyond primary care is, however, still lacking.Factors associated with adverse inpatient outcomes also need further investigation.
The JBDS guideline on inpatient care of frail older adults with diabetes recommends that attempts should be made to access previous glycated haemoglobin (HbA1c) readings carried out in the last 6-12 months. 11This will help identify those with the highest risk of inpatient hypoglycaemia -people with an HbA1c of less than 7% (53 mmol/mol). 12If no recent HbA1c readings are available, the guideline recommends carrying these out during the admission.As admission to the hospital represents an opportunity for medication review in people with diabetes and frailty, assessing HbA1c upon admission could improve the rate of deintensification and avoid treatment inertia in this group of patients.
The aims of this audit were (i) to identify the proportion of patients who had their HbA1c assessed during their inpatient stay if they had not been carried out six months prior to the admission, (ii) to assess the rates of inpatient deintensification including those with a higher risk of hypoglycaemia, and (iii) to describe the characteristics and outcomes of

Table 1
Tools to detect frailty in people with diabetes as recommended by the Joint British Diabetes Societies (JBDS).Adapted from the JBDS Inpatient care of frail older adults with diabetes. 11

Assessment tool
Fried score 21 Consists of five measures: i. Shrinking: Weight loss (unintentional), sarcopenia (loss of muscle mass.Defined as > 10lbs weight loss in the prior year.ii.Weakness: defined as grip strength in the lowest 20% by gender and body mass index.iii.Self-reported poor endurance or exhaustion iv.Slowness: walking time/15 feet, slowest 20% by gender and body mass index v.Calories per week < 383 in men and < 270 in women ≥ 3 positive criteria: frail phenotype 1 or 2 positive phenotypes: Intermediate or pre-frail Clinical frailty score (CFS) 4 Nine-point visual descriptions of physical functioning and care needs that are easy to implement in routine clinical practice.
CFS 5 = Mild frailty: people with evidence of slowing and need help with high order instrumental activities of daily living CFS 6 = Moderate frailty: people who need help with all outside activities and with keeping the house.Problems with stairs, bathing and minimal assistant with dressing CFS 7 = Severe frailty: completely dependent for personal care CFS 8 = Very severe frailty: completely dependent for personal care; approaching end of life CFS 9 = Terminally ill: life expectancy of < 6months, who are not otherwise living with severe frailty FRAIL score 22 Five components including: (0 = Best; 5 = Worst) i. Fatigue ii.Resistance iii.Ambulation iv.Illness v. Loss of weight Score 3-5 = frailty Score 1-2 = pre-frailty 0 = robust health status PRISMA 7 questionnaire 23 Seven simple questions: i. > 85 years old?ii.Male? iii.Any problems that limit activities?iv.Require help on a regular basis?v. Any health problems that require person to stay at home? vi.If need help, can you count on somebody close?vii.Regularly uses stick, walker or wheelchair to move about?More than 3 "Yes " -increased risk for frailty and require further clinical review people with diabetes and moderate/severe frailty admitted to the hospital.

Study population and data source
All patients who were admitted to the University Hospitals of Leicester NHS Trust underwent diabetes assessment by frontline clinical staff who ascertained patients' diabetes status and type of diabetes either by asking the patients and/or looking at the patient's electronic record system.CFS was also calculated for every patient on admission and these data were incorporated into the patients' electronic chart.Admission medications were ascertained by clinical pharmacists by asking the patients, carers, and/or by accessing their primary care electronic medical records ( Fig. 1 ).
Retrospective electronic charts were reviewed in all patients with diabetes and CFS ≥ 6 who were discharged from the medical unit at the Leicester Royal Infirmary, University Hospitals of Leicester NHS Trust.Patients were included if they had CFS ≥ 6 and a history of diabetes ascertained by their past medical history.Data on age, sex, ethnicity, CFS, weight, height, body mass index (BMI, calculated as weight in kilogrammes divided by height in square metres), diabetes-related complications [retinopathy, chronic kidney disease/nephropathy, peripheral arterial disease/amputation, neuropathy, heart failure (heart failure with preserved ejection fraction, heart failure with reduced ejection fraction and congestive heart failure), ischaemic heart disease (stable or unstable angina, previous myocardial infarctions), cerebrovascular disease (previous transient ischaemic attack or previous stroke), hypertension, cognitive impairment/dementia, and dyslipidaemia], and background glucose-lowering medications were collected.Levels of HbA1c on admission, defined as HbA1c levels that were checked prior to admission, and the dates of measurement were also collected.The dates of HbA1c measurement were then used to assess if the HbA1c levels were checked six months prior to the admission date.If the patient was on metformin, information regarding vitamin B12 measurement on admission including the date assessed was collected.Following discharge, the discharge letter and discharge medications were reviewed and compared to the admission medications to assess for any deintensification during their inpatient stay.Data regarding patients' presenting complaints were checked to ascertain if this episode of admission was due to a fall.Data on inpatient hypoglycaemia, length of stay and 30-day readmission rates were also collected.
This study received registration and approval as an audit and quality improvement programme (QIP) at the University Hospitals of Leicester (QIP reference number: 12278).The UHL QIP committee determined that further ethical approval was not needed since this study pertains to patient improvement within our institution.

Definition of patient parameters and outcomes
Overtreatment was defined as people with admission HbA1c of < 7% (53 mmol/mol) with at least one glucose-lowering medication.Other overtreatment groups were also created with different HbA1c thresholds [ < 7.5% (59 mmol/mol), < 8.0% (64 mmol/mol), and < 8.5% (69 mmol/mol)].These HbA1c levels were chosen due to the heterogeneity of the definitions of overtreatment in older people with diabetes.Any inpatient episode of hypoglycaemia was defined as any capillary blood glucose reading of < 4.0 mmol/L during their inpatient stay, whereas severe hypoglycaemia was defined as a capillary blood glucose of < 3.0 mmol/L.Inpatient deintensification was defined as a decrease or discontinuation of any glucose-lowering medication without adding another drug, or a reduction in the total daily dose of insulin or a sulphonylurea with or without adding a drug with a lower risk of hypoglycaemia.The change of insulin regimen to insulin with a better hypoglycaemic profile was also considered deintensification.Ethnicity status was categorised into White and non-White (Black -African, Black -Caribbean, Asian -Indian, Asian -Bangladesh, Asian -Pakistan, Asian -Chinese, Asian -Others) due to the small sample of individuals of non-White ethnicities.

Statistical analysis
Shapiro-Wilk test was used to check for the distribution of the continuous variables.The median and interquartile range (IQR) are presented due to the variables' non-normality.Descriptive statistics are presented for the categorial variables and are presented as absolute numbers and proportions.Chi-squared test and Mann-Whitney test were conducted to assess the differences between groups for categorical and continuous data, respectively.Multivariate logistic regression was used to assess for any associations of patient factors with inpatient hypoglycaemia, deintensification, and inpatient mortality.Odds ratios are presented with a 95% confidence interval (CI) and models are adjusted for age, sex, ethnicity, CFS, background co-morbidities, background medications, admission HbA1c, and reason for admission.Simple linear regression was used to assess for any association between patient factors and length of stay.Final multivariate linear regression models included age, CFS, BMI, and insulin use.The statistical significance threshold was 2-sided p = 0.05.Data were analysed using Stata/SE 17.0 for Mac (Texas, US).

Baseline characteristics and rates of overtreatment
A total of 665 people with diabetes and CFS ≥ 6 was included in our analysis.Median age was 79 years (71-86 years).The majority of people were White (75.8%,n = 504/665) with a median CFS of 6 (6-7).96.4%  2 , Appendix 1).BMI was slightly higher in people who were not overtreated compared to the overtreated (26.5 kg/m 2 vs 25.0 kg/m 2 , n = 0.021).People who were overtreated were less likely to have retinopathy and be on medi-cations such as metformin, sulphonylureas, insulin, and DPP4i.People who were overtreated had fewer episodes of inpatient hypoglycaemia compared to those who were not overtreated.There were no statistically significant differences in other inpatient outcomes ( Table 2 ).

Audit of inpatient assessments and rates of deintensification
68.1% (n = 453/665) of people had their HbA1c assessed 6 months prior to the admission.Of those who did not have their HbA1c checked in the preceding 6 months, only 9.0% (n = 19/212) had it checked during the admission.In people who were on metformin, only 55.1% (n = 136/247) had their vitamin B12 levels checked in the last 12 months.The rate of deintensification was 19.1% (n = 119/625); in the overtreated group deintensification rate was lower, compared to the not overtreated group (14.4% vs 23.7%, p = 0.003).Of those who were on insulin and/or Fig. 2. Inpatient assessment and management of people with diabetes and moderate/severe frailty.* people with diabetes and frailty with HbA1c < 7% (53mmol/mol) who are on insulin/sulphonlyurea and/or inpatient hypoglycaemia.sulphonylurea, HbA1c < 7.0% (53 mmol/mol) and/or hypoglycaemia, only 34.3% (n = 74/216) were deintensified ( Fig. 2 ).
After adjusting for other variables, ischaemic heart disease was associated with higher odds of readmission to the hospital in a month (aOR: 1.67, 95% CI: 1.07-2.61).People who were aged ≥ 65 years were less likely to be readmitted, compared to those aged < 65 years (aOR: 0.46, 95% CI: 0.25-0.85)(Appendix 9).As for the readmissions, those with initial admission due to a fall were more likely to be readmitted in a month due to a fall (aOR: 4.02, 95% CI: 1.04-15.5).Metformin appeared to decrease the odds of one-month readmission due to a fall (aOR: 0.22, 95% CI: 0.05-0.92)(Appendix 10).

Discussion
Our results show suboptimal assessment of HbA1c in people with diabetes and moderate/severe frailty admitted to the hospital.The rate of deintensification in people with a high risk of falls and hypoglycaemia was also low, suggesting the treatment inertia in this population.Additionally, the inpatient hypoglycaemia rate was unacceptably high, possibly due to pre-admission treatment inertia, and correlated with insulin therapy and non-White ethnicity.Inpatient hypoglycaemic episodes were also associated with a prolonged stay.Factors associated with inpatient mortality included being overtreated and having an episode of inpatient hypoglycaemia.
Regrettably, our audit has shown that the JBDS recommendation for HbA1c measurements 11 in people with diabetes and frailty is not part of routine clinical practice, causing an incomplete assessment of older people with diabetes and frailty.Furthermore, the absence of HbA1c means missed chances for deintensification during hospitalisation, perpetuating therapeutic inertia.As part of the inpatient assessment of people with diabetes and moderate/severe frailty, identifying those with the highest risk of morbidity and mortality from overtreatment is also crucial.Considering the importance of individualised care in the older population, several guidelines for HbA1c targets in older people with diabetes have been published.Depending on the recommendations, the definition of overtreatment varies by HbA1c ranging from < 7.0% to < 8.5% (53-69 mmol/mol) with or without glucose-lowering medication. 13Our chosen target of HbA1c < 7.0% (53 mmol/mol) with at least one glucose-lowering medication was conservative as it allowed us to identify the lowest rate of deintensification in these patients upon admission to the hospital.Furthermore, considering the different definitions used for overtreatment in our study, the HbA1c threshold of < 7.0% (53 mmol/mol) seems to be the only group that was independently associated with higher odds of inpatient mortality.However, it is important to note that HbA1c levels may be inaccurate in conditions such as anaemia and iron deficiency hence reliance on HbA1c may not be appropriate in all patients. 14ur findings show that only 14.4% of overtreated people with diabetes and moderate/severe frailty were deintensified during admission.This could be due to the low rate of HbA1c assessment and other confounding factors such as stress hyperglycaemia or patient preferences that prevented deintensification.In people who were on insulin and/or  95% CI = confidence interval; CFS = clinical frailty score; BMI = body mass index sulphonylurea with HbA1c < 7.0% (53 mmol/mol) and/or inpatient hypoglycaemia, the deintensification rate was slightly higher at 34.3%.No immediate benefit was seen with inpatient deintensification such as a reduced one-month readmission rate or reduced readmission due to falls.Observing such benefits is probably premature at this duration and the low sample size of readmitted people may also play a role.Regardless, reducing polypharmacy has been shown to benefit people who are frail independent of HbA1c levels. 10The evidence for the benefits of deintensification in older people with diabetes and frailty is also emerging with studies suggesting the benefits of deintensification outweigh the harm regardless of the co-morbidities. 7 , 15Moreover, episodes of hypoglycaemia in older people with diabetes and frailty are associated with increased mortality and morbidity including increased cardiovas-cular risks further highlighting the need for deintensification especially for those with the highest risk. 16 , 17In line with this, our findings also showed that people with inpatient hypoglycaemia who were overtreated had higher odds of inpatient mortality.
On the other hand, several studies have been conducted to assess the rates of deintensification in older people with diabetes.However, most of them did not consider frailty status and were conducted in primary care setting. 8 , 9In an Australian study of older people with type 2 diabetes who presented to the hospital with severe hypoglycaemia, the deintensification rate was found to be less than 50% within 100 days of presentation. 10People with frailty were more likely to be deintensified compared to those without.However, the study was only limited to people older than 65 years hence omitting younger people with frailty. 10In contrast, our study provided new evidence in younger people with diabetes and moderate/severe frailty with only 19.7% of deintensification in this population, similar to older people.Evidence-based interventions and guidance for inpatient assessment and deintensification of people with diabetes and moderate/severe frailty are needed to improve the care of such patients and reduce the burden of primary care.Our institution is developing a quality improvement project to guide the assessment and deintensification for frail people with diabetes ( Fig. 3 ).This responsibility falls to the managing physicians, but the diabetes inpatient team (DIT) plays a crucial role in identifying highrisk patients and assisting with complex cases, particularly those involving multiple treatments or insulin regime adjustment that might be indicated.
In our study, admission HbA1c and being overtreated were not associated with inpatient hypoglycaemia which could be explained by the low proportion of people being on agents with a higher risk of hypoglycaemia.Inpatient hypoglycaemia appears to be one of the most important factors that impact inpatient outcomes in people with diabetes and frailty.In our study, having inpatient hypoglycaemia increased the odds of inpatient mortality and was associated with prolonged length of stay.Insulin therapy and non-White ethnicity were associated with developing inpatient hypoglycaemia.9][20] Our study showed for the first time an increased odds of inpatient hypoglycaemia in ethnic minorities with diabetes and frailty.It is, therefore, important to prevent inpatient hypoglycaemia with early medication review and early deintensification, especially in non-White populations who seem to be at higher risk.This could help to decrease morbidity and mortality as well as reduce the ethnic disparities in people with diabetes and frailty admitted to the hospital.

Strengths and limitations
This study has several strengths.We included all patients discharged in the past year hence minimised the selection bias from the population.Our sample is also ethnically diverse which can be reflective of the general population in the United Kingdom.We also used a validated measurement of frailty which enabled us to include younger patients with frailty which was not done in previous studies.Our analyses also investigated several factors including age, CFS, background medications and co-morbidities which could also impact the measured outcomes.
One of the limitations of this study is the single-centredness making our deintensification rate not generalisable as this could be centrespecific.However, the rates of hypoglycaemia and its association with prolonged length of stay can be generalised as these are usually unaffected by the setting.Lastly, we also did not consider factors such as uncontrolled hyperglycaemia during admission and patient preference as these factors could potentially impact deintensification rates.

Conclusion
Our study shows suboptimal assessment of HbA1c and a low rate of deintensification in people with diabetes and moderate/severe frailty including in patients with a high risk of falls and hypoglycaemia.We also identified factors associated with inpatient outcomes, most importantly, inpatient hypoglycaemia, further highlighting the importance of hypoglycaemia prevention and early inpatient deintensification.Finally, an evidenced-based stratification tool to identify patients at the highest risk of hypoglycaemia and overtreatment is urgently needed to improve patient care and decrease inpatient morbidity and mortality.

Fig. 1 .
Fig. 1.Retrospective data collection for people admitted with diabetes and moderate/severe frailty.

Fig. 3 .
Fig. 3. Inpatient guidance for assessment and deintensification in people with diabetes and frailty.

Table 2
Baseline characteristics of inpatients with diabetes and moderate/severe frailty stratified by HbA1c status.

Table 4
Multiple linear regression model showing association between inpatient hypoglycaemia and length of stay.